Gemcitabine/Capecitabine for Biliary Tract Cancer: Patient-Reported Outcomes
Gemcitabine/Capecitabine for Biliary Tract Cancer: Patient-Reported Outcomes
Abstract & Commentary
By William B. Ershler, MD
Synopsis: Chemotherapy for advanced biliary tract cancers has been of only marginal value, in terms of objective response rates and improved survival. To assess whether chemotherapy with gemcitabine and capecitabine could effect improved quality of life and diminished symptoms, Koeberle et al performed a phase II trial using patient reported outcomes such as pain relief, physical performance and change in body weight, as outcome measures. The gemcitabine/ capecitabine combination did result in a significant improvement in these measures in about one-third of cases, and stability in those measures in another one-third. In terms of palliation, this combination appears to an effective choice.
Source: Koeberle D, et al Patient-reported outcomes of patients with advanced biliary tract cancers receiving gemcitabine plus capecitabine: a multicenter phase II trial of the Swiss Group for Clinical Cancer Research. J Clin Oncol. 2008;26:3702-3708.
Biliary tract carcinomas are uncommon, and the role for chemotherapy, even in the palliative setting, is not established. Nonetheless, there have been reports of several trials with agents such as gemcitabine alone,1 or in combination with mitomycin,2 cisplatin,3 or capecitabine,4 and response rates have varied from 10%-35%. The current trial was designed to evaluate the effects of palliative chemotherapy with gemcitabine plus capecitabine (GemCap) on patient-reported outcomes determined using clinical benefit response (CBR) and quality-of-life (QOL) measures in patients with advanced biliary tract cancer. Clinical benefit response (CBR) required predefined improvements in pain (either intensity or analgesic use), performance (Karnofsky) score, or weight over a four-week span.
Eligibility requirements included cancer-related symptoms, as well as at least one of the following: impaired Karnofsky performance score (60 to 80), average analgesic consumption of at least 10 mg of morphine equivalents per day, and average pain intensity score (by linear analog scale) of at least 20 mm out of 100 mm. Treatment consisted of oral capecitabine 650 mg/m2 twice daily on days 1-14 plus gemcitabine 1,000 mg/m2 as a 30-minute infusion on days 1 and 8 every three weeks until progression. The primary endpoint was the number of patients categorized as having a CBR or stable CBR (SCBR) during the first three treatment cycles.
Forty-four patients were enrolled (bile duct cancer, n = 36; gallbladder cancers, n = 8). The main grade 3 or 4 adverse events included hematologic toxicity and fatigue. After three cycles, 36% of patients achieved a CBR, and 34% achieved SCBR. Over the full course of treatment, 57% of patients achieved a CBR, and 18% achieved an SCBR. Improved QOL was observed in patients with a CBR or SCBR. By standard criteria, the objective response rate was 25%. Median time to progression and over-all survival times were 7.2 months and 13.2 months, respectively.
Commentary
Biliary tract carcinomas remain a major challenge, for although uncommon, survival is measured in months and interventions other than surgery have shown little objective benefit. Chemotherapy with gemcitabine or capecitabine, alone, or in combination has been shown to be of only slight objective benefit in terms of survival. However, in terms of palliation and quality of life, it was reasonable to think these drugs might have benefit. Using standard phase II design but incorporating a novel assessment method which included patient reported-outcome measures, such as pain level and physical function, Koeberle et al were able to demonstrate the GemCap combination was both well tolerated and effective, leading to a high CBR rate. This is useful information, particularly in the palliative setting, which is so often the case in patients with biliary carcinoma.
For clinicians, it is useful to know that under controlled circumstances, patients with advanced biliary carcinoma achieved improvement in function and quality of life by treatment with a relatively well-tolerated regimen. For clinical investigators, the outcome measures employed is worth a look. Often, clinicians intending to provide palliation for patients with advanced disease can only rely on published clinical trials that measure success only in terms of response rate or added weeks of life. The patient-reported outcome measures, such as employed in this trial, is an excellent template to be considered for the assessment of palliative treatment of cancer.
References
1. Gebbia V, et al. Treatment of inoperable and/or metastatic biliary tree carcinomas with single-agent gemcitabine or in combination with levofolinic acid and infusional fluorouracil: results of a multicenter phase II study. J Clin Oncol. 2001;19:4089-4091.
2. Raderer M, et al. Two consecutive phase II studies of 5-fluorouracil/leucovorin/mitomycin C and of gemcitabine in patients with advanced biliary cancer. Oncology. 1999;56:177-180.
3. Taieb J, et al. Optimization of 5-fluorouracil (5-FU)/cisplatin combination chemotherapy with a new schedule of leucovorin, 5-FU and cisplatin (LV5FU2-P regimen) in patients with biliary tract carcinoma. Ann Oncol. 2002;13:1192-1196.
4. Knox JJ, et al. Combining gemcitabine and capecitabine in patients with advanced biliary cancer: a phase II trial. J Clin Oncol. 2005;23:2332-2338.
Chemotherapy for advanced biliary tract cancers has been of only marginal value, in terms of objective response rates and improved survival. To assess whether chemotherapy with gemcitabine and capecitabine could effect improved quality of life and diminished symptoms, Koeberle et al performed a phase II trial using patient reported outcomes such as pain relief, physical performance and change in body weight, as outcome measures. The gemcitabine/ capecitabine combination did result in a significant improvement in these measures in about one-third of cases, and stability in those measures in another one-third. In terms of palliation, this combination appears to an effective choice.Subscribe Now for Access
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